DD153840A5 - Verfahren zur herstellung von neuartigen substituierten pyrazol(1,5-a)pyrimidinen - Google Patents

Verfahren zur herstellung von neuartigen substituierten pyrazol(1,5-a)pyrimidinen Download PDF

Info

Publication number: DD153840A5
Authority: DD; German Democratic Republic
Prior art keywords: pyrazolo; pyridyl; item; mixture; hours
Prior art date: 1979-07-09

Application number

DD80222505A

Other languages

German (de)

English (en)

Inventor

John P Dusza

Jay D Albright

Original Assignee

American Cyanamid Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1979-07-09

Filing date

1980-07-09

Publication date

1982-02-03

1980-07-09 Application filed by American Cyanamid Co filed Critical American Cyanamid Co

1982-02-03 Publication of DD153840A5 publication Critical patent/DD153840A5/de

Links

NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 title 1
238000004519 manufacturing process Methods 0.000 title 1
150000003230 pyrimidines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 58
238000000034 method Methods 0.000 claims abstract description 26
238000002360 preparation method Methods 0.000 claims abstract description 10
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 78
-1 cyano, cyanomethyl Chemical group 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 17
125000004432 carbon atom Chemical group C* 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 7
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
150000002431 hydrogen Chemical group 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
239000000460 chlorine Chemical group 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000011737 fluorine Chemical group 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000004494 ethyl ester group Chemical group 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
239000011593 sulfur Substances 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims 2
125000001309 chloro group Chemical group Cl* 0.000 claims 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
125000001246 bromo group Chemical group Br* 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000004076 pyridyl group Chemical group 0.000 claims 1
150000003839 salts Chemical class 0.000 claims 1
239000002249 anxiolytic agent Substances 0.000 abstract description 5
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 abstract description 2
210000003169 central nervous system Anatomy 0.000 abstract description 2
238000011084 recovery Methods 0.000 abstract description 2
LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 abstract 2
PVRYOKQFLBSILA-UHFFFAOYSA-N 1-(6-methylpyridin-3-yl)ethanone Chemical compound CC(=O)C1=CC=C(C)N=C1 PVRYOKQFLBSILA-UHFFFAOYSA-N 0.000 abstract 1
OOPDMPGQQKKAKO-UHFFFAOYSA-N 2-ethyl-7-pyridin-3-ylpyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C=1C=NC2=C(C#N)C(CC)=NN2C=1C1=CC=CN=C1 OOPDMPGQQKKAKO-UHFFFAOYSA-N 0.000 abstract 1
DUUCTQDWBLHQEJ-UHFFFAOYSA-N 3-(dimethylamino)-1-(6-methylpyridin-3-yl)prop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=C(C)N=C1 DUUCTQDWBLHQEJ-UHFFFAOYSA-N 0.000 abstract 1
HSJKYKFHQPQVTJ-UHFFFAOYSA-N 3-chloro-7-(6-methylpyridin-3-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=NC(C)=CC=C1C1=CC=NC2=C(Cl)C=NN12 HSJKYKFHQPQVTJ-UHFFFAOYSA-N 0.000 abstract 1
ZQJQHZKZIQYVIK-UHFFFAOYSA-N 4-chloro-1h-pyrazol-5-amine Chemical compound NC=1NN=CC=1Cl ZQJQHZKZIQYVIK-UHFFFAOYSA-N 0.000 abstract 1
239000000203 mixture Substances 0.000 description 100
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 91
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
229960000583 acetic acid Drugs 0.000 description 42
238000002844 melting Methods 0.000 description 38
230000008018 melting Effects 0.000 description 38
239000002904 solvent Substances 0.000 description 37
239000012362 glacial acetic acid Substances 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
239000000243 solution Substances 0.000 description 26
239000013078 crystal Substances 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
238000012360 testing method Methods 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
238000010992 reflux Methods 0.000 description 14
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
241000700159 Rattus Species 0.000 description 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 10
239000000391 magnesium silicate Substances 0.000 description 10
229910052919 magnesium silicate Inorganic materials 0.000 description 10
235000019792 magnesium silicate Nutrition 0.000 description 10
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
MZLRFUCMBQWLNV-UHFFFAOYSA-N 3-(dimethylamino)-1-pyridin-3-ylprop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=CN=C1 MZLRFUCMBQWLNV-UHFFFAOYSA-N 0.000 description 7
230000027455 binding Effects 0.000 description 7
239000011734 sodium Substances 0.000 description 7
FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
229920001223 polyethylene glycol Polymers 0.000 description 6
230000035939 shock Effects 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
230000000949 anxiolytic effect Effects 0.000 description 5
125000001072 heteroaryl group Chemical group 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000000575 pesticide Substances 0.000 description 5
239000011591 potassium Substances 0.000 description 5
229910052700 potassium Inorganic materials 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
229940049706 benzodiazepine Drugs 0.000 description 4
230000037396 body weight Effects 0.000 description 4
239000002775 capsule Substances 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
229910052744 lithium Inorganic materials 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
229960005152 pentetrazol Drugs 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 3
UJWKFJHUNQWGDB-UHFFFAOYSA-N 3-(dimethylamino)-1-(5-methylpyridin-2-yl)prop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=C(C)C=N1 UJWKFJHUNQWGDB-UHFFFAOYSA-N 0.000 description 3
JYNBBGZIKXUJAK-UHFFFAOYSA-N 3-(dimethylamino)-1-(furan-3-yl)prop-2-en-1-one Chemical compound CN(C)C=CC(=O)C=1C=COC=1 JYNBBGZIKXUJAK-UHFFFAOYSA-N 0.000 description 3
JZGHSXBVKSMAKH-UHFFFAOYSA-N 3-(dimethylamino)-1-pyridin-4-ylprop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=NC=C1 JZGHSXBVKSMAKH-UHFFFAOYSA-N 0.000 description 3
208000019901 Anxiety disease Diseases 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
239000003963 antioxidant agent Substances 0.000 description 3
239000002027 dichloromethane extract Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
YPXGHKWOJXQLQU-UHFFFAOYSA-N ethyl 5-amino-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1N YPXGHKWOJXQLQU-UHFFFAOYSA-N 0.000 description 3
229960004285 fomepizole Drugs 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
VDNKJMUNLKAGAM-UHFFFAOYSA-N 1-pyridin-3-ylpropan-1-one Chemical compound CCC(=O)C1=CC=CN=C1 VDNKJMUNLKAGAM-UHFFFAOYSA-N 0.000 description 2
FPQMUQPPAYCAME-UHFFFAOYSA-N 2-Acetyl-6-methylpyridine Chemical compound CC(=O)C1=CC=CC(C)=N1 FPQMUQPPAYCAME-UHFFFAOYSA-N 0.000 description 2
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
HJFLVSLLNSHDLD-UHFFFAOYSA-N 3-(dimethylamino)-1-(6-methylpyridin-2-yl)prop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=CC(C)=N1 HJFLVSLLNSHDLD-UHFFFAOYSA-N 0.000 description 2
BWERGHWJEBQNQV-UHFFFAOYSA-N 3-(dimethylamino)-1-pyridin-2-ylprop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=CC=N1 BWERGHWJEBQNQV-UHFFFAOYSA-N 0.000 description 2
CDOOQLDZGMQWQC-UHFFFAOYSA-N 3-(dimethylamino)-1-thiophen-3-ylprop-2-en-1-one Chemical compound CN(C)C=CC(=O)C=1C=CSC=1 CDOOQLDZGMQWQC-UHFFFAOYSA-N 0.000 description 2
UJLNPEBSWFVERJ-UHFFFAOYSA-N 3-(dimethylamino)-2-methyl-1-pyridin-3-ylprop-2-en-1-one Chemical compound CN(C)C=C(C)C(=O)C1=CC=CN=C1 UJLNPEBSWFVERJ-UHFFFAOYSA-N 0.000 description 2
ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
241000167854 Bourreria succulenta Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
206010053398 Clonic convulsion Diseases 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
238000007171 acid catalysis Methods 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000036506 anxiety Effects 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
235000019693 cherries Nutrition 0.000 description 2
230000001143 conditioned effect Effects 0.000 description 2
239000003433 contraceptive agent Substances 0.000 description 2
230000002254 contraceptive effect Effects 0.000 description 2
238000001816 cooling Methods 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
229960003529 diazepam Drugs 0.000 description 2
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
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239000007789 gas Substances 0.000 description 2
244000144980 herd Species 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
230000010807 negative regulation of binding Effects 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
229940068968 polysorbate 80 Drugs 0.000 description 2
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
229930192474 thiophene Natural products 0.000 description 2
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238000005303 weighing Methods 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
LHYWOHDQEGXUCG-UHFFFAOYSA-N 1-(6-methylpyridin-3-yl)prop-2-en-1-one Chemical compound C(=O)(C1=CN=C(C)C=C1)C=C LHYWOHDQEGXUCG-UHFFFAOYSA-N 0.000 description 1
GCCKHXWBNPBUOD-UHFFFAOYSA-N 1-(furan-3-yl)ethanone Chemical compound CC(=O)C=1C=COC=1 GCCKHXWBNPBUOD-UHFFFAOYSA-N 0.000 description 1
INOGLHRUEYDAHX-UHFFFAOYSA-N 1-chlorobenzotriazole Chemical compound C1=CC=C2N(Cl)N=NC2=C1 INOGLHRUEYDAHX-UHFFFAOYSA-N 0.000 description 1
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ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
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HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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229940033663 thimerosal Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

DD80222505A 1979-07-09 1980-07-09 Verfahren zur herstellung von neuartigen substituierten pyrazol(1,5-a)pyrimidinen DD153840A5 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US5594179A	1979-07-09	1979-07-09
US06/124,686 US4281000A (en)	1979-07-09	1980-02-26	Substituted pyrazolo (1,5-a)pyrimidines and their use as anxiolytic agents

Publications (1)

Publication Number	Publication Date
DD153840A5 true DD153840A5 (de)	1982-02-03

Family

ID=26734791

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD80222505A DD153840A5 (de)	1979-07-09	1980-07-09	Verfahren zur herstellung von neuartigen substituierten pyrazol(1,5-a)pyrimidinen

Country Status (12)

Country	Link
US (1)	US4281000A (2)
EP (1)	EP0025819B1 (2)
AR (1)	AR227766A1 (2)
AU (1)	AU536081B2 (2)
CA (1)	CA1140125A (2)
DD (1)	DD153840A5 (2)
DE (1)	DE3065270D1 (2)
GR (1)	GR70075B (2)
HU (1)	HU182153B (2)
IL (1)	IL60330A (2)
PL (1)	PL126652B1 (2)
YU (1)	YU172280A (2)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU557300B2 (en) *	1982-03-16	1986-12-18	Farmitalia Carlo Erba S.P.A.	Substituted 1h-pyrazolo(1,5-alpha)pyrimidines and processes for their preparation
ZA831407B (en) *	1982-03-25	1983-11-30	Erba Farmitalia	Substituted ethenyl derivatives of 1h-pyrazolo(1,5-a)pyrimidine and process for their preparation
US4444774A (en) *	1982-07-29	1984-04-24	American Cyanamid Company	7-Heteroaryl[1,2,4]triazolo[1,5-a]pyrimidines
NZ208554A (en) *	1983-06-23	1987-06-30	American Cyanamid Co	(aryl and heteroaryl)-(7-(aryl and heteroaryl)-pyrazolo (1,5-a) pyrimidin-3-yl)-methanone derivatives and pharmaceutical compositions
US4654347A (en) *	1983-06-23	1987-03-31	American Cyanamid Company	Aryl and heteroaryl[[7-(3-disubstituted amino)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]methanones
US4626538A (en) *	1983-06-23	1986-12-02	American Cyanamid Company	[7-(3-disubstituted amino)phenyl]pyrazolo[1,5-a]pyrimidines
NZ208555A (en) *	1983-06-23	1987-06-30	American Cyanamid Co	(3-amino-1h-pyrazol-4-yl)-arylmethanone derivatives
US4521422A (en) *	1983-06-23	1985-06-04	American Cyanamid Company	Aryl and heteroaryl[7-(aryl and heteroaryl)pyrazolo[1,5-a]pyrimidin-3-yl]methanones
US4576943A (en) *	1984-10-09	1986-03-18	American Cyanamid Company	Pyrazolo[1,5-a]pyrimidines
GB8610531D0 (en) *	1986-04-30	1986-06-04	Fbc Ltd	Herbicides
EP0264773A1 (en) *	1986-10-16	1988-04-27	American Cyanamid Company	4,5-dihydro and 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidines
US5013737A (en) *	1988-02-22	1991-05-07	American Cyanamid Company	2,4,8-Trisubstituted-3H,6H-1,4,5A,8A-tetraazaacenaphtylene-3,5-(4H)-diones and 2,4-8-trisubstituted-4,5-dihydro-5-thioxo-3H,6H-1,4,5A,8A-tetrazaacenaphthylen-3-ones
US5059709A (en) *	1990-11-13	1991-10-22	American Cyanamid Company	Process for the synthesis of α-[(dialkylamino)substituted-methylene]-β-oxo-(substituted)propanentriles
DE4333705C2 (de) *	1993-10-02	2003-10-30	Guenter Ege	Arylmethylsubstituierte Pyrazolo-azine, insbesondere 3-Arylmethylpyrazolo[1,5-a]pyrimidine und Verfahren zur Herstellung von 8-Arylmethyl-pyrazolo[5,1-c][1,2,4]triazinen
US5538977A (en) *	1995-03-17	1996-07-23	American Cyanamid Company	3-Substituted-7-[3-(imidazol-1-yl)phenyl]-pyrazolo[1,5-a]pyrimidines
US5714607A (en) *	1995-12-01	1998-02-03	American Cyanamid Company	Process improvement in the synthesis of N- 3-(3-cyano-pyrazolo 1,5-a!pyrimidin-7-yl)phenyl!-N-ethylacetamide
WO2000059908A2 (en) *	1999-04-06	2000-10-12	Du Pont Pharmaceuticals Company	Pyrazolopyrimidines as crf antagonists
RU2183610C1 (ru) *	2000-11-15	2002-06-20	Институт молекулярной генетики РАН	Высокомеченный тритием n-[3-(3-цианопиразоло[1,5-а]пиримидин-7-ил)фенил]-n-этилацетамид
GB0202873D0 (en) *	2002-02-07	2002-03-27	Novartis Ag	Organic compounds
TW200719895A (en) *	2005-05-26	2007-06-01	Wyeth Corp	Method for the treatment of noise phobia in companion animals
US20100029657A1 (en) *	2008-02-29	2010-02-04	Wyeth	Bridged, Bicyclic Heterocyclic or Spiro Bicyclic Heterocyclic Derivatives of Pyrazolo[1, 5-A]Pyrimidines, Methods for Preparation and Uses Thereof
WO2013035102A1 (en)	2011-09-05	2013-03-14	Natco Pharma Limited	Processes for the preparation of imatinib base and intermediates thereof
US11167081B2 (en)	2016-06-16	2021-11-09	Smiths Medical Asd, Inc.	Assemblies and methods for infusion pump system administration sets
CN117659025A (zh) *	2017-10-30	2024-03-08	科罗拉多州立大学董事会法人团体	Toll样受体8（tlr8）特异性拮抗剂及其制备方法和用途
US12479816B2 (en)	2019-02-08	2025-11-25	University of Pittsburgh—of the Commonwealth System of Higher Education	20-HETE formation inhibitors
UY39482A (es)	2020-10-23	2022-05-31	Ildong Pharmaceutical Co Ltd	Compuestos moduladores del cftr, composiciones y usos de estos
CN112745300A (zh) *	2021-01-21	2021-05-04	杭州浙中医药科技有限公司	一种制备n-(5-羧基-2-甲基苯基)-4-(3-吡啶)-2-嘧啶胺的方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3157655A (en) *	1962-05-18	1964-11-17	Shionogi & Co	Pyrazolopyrimidine derivative
BE786611A (fr) *	1971-08-16	1973-01-22	Int Chem & Nuclear Corp	Nouveaux inhibiteurs de xanthine-oxydase et leur procede de preparatio
US3907799A (en) *	1971-08-16	1975-09-23	Icn Pharmaceuticals	Xanthine oxidase inhibitors
US3925385A (en) *	1972-04-20	1975-12-09	Icn Pharmaceuticals	6-Carbethoxy-3,7-disubstitutedpyrazolo{8 1,5a{9 pyrimidines
BE792533A (fr) *	1971-12-09	1973-06-08	Int Chem & Nuclear Corp	Nouvelles pyrazolo (1,5a) pyrimidines et leur procede de preparation
US4093617A (en) *	1974-11-12	1978-06-06	Icn Pharmaceuticals, Inc.	3,5,7-Trisubstituted pyrazolo[1,5-a]pyrimidines
US4178449A (en) *	1978-04-17	1979-12-11	American Cyanamid Company	Pyrazolo[1,5-a]pyrimidines and imidazo-[1,5-a]pyrimidines

1980
- 1980-02-26 US US06/124,686 patent/US4281000A/en not_active Expired - Lifetime
- 1980-06-16 DE DE8080103342T patent/DE3065270D1/de not_active Expired
- 1980-06-16 EP EP80103342A patent/EP0025819B1/en not_active Expired
- 1980-06-17 IL IL60330A patent/IL60330A/xx unknown
- 1980-06-19 GR GR62253A patent/GR70075B/el unknown
- 1980-06-23 AU AU59517/80A patent/AU536081B2/en not_active Expired - Fee Related
- 1980-06-25 CA CA000354774A patent/CA1140125A/en not_active Expired
- 1980-07-02 YU YU01722/80A patent/YU172280A/xx unknown
- 1980-07-08 PL PL1980225541A patent/PL126652B1/pl unknown
- 1980-07-09 HU HU801714A patent/HU182153B/hu unknown
- 1980-07-09 DD DD80222505A patent/DD153840A5/de unknown
1982
- 1982-07-01 AR AR281605A patent/AR227766A1/es active

Also Published As

Publication number	Publication date
YU172280A (en)	1983-02-28
US4281000A (en)	1981-07-28
EP0025819A1 (en)	1981-04-01
IL60330A0 (en)	1980-09-16
EP0025819B1 (en)	1983-10-12
PL126652B1 (en)	1983-08-31
HU182153B (en)	1983-12-28
DE3065270D1 (en)	1983-11-17
GR70075B (2)	1982-07-27
AU536081B2 (en)	1984-04-19
AR227766A1 (es)	1982-12-15
IL60330A (en)	1984-05-31
CA1140125A (en)	1983-01-25
AU5951780A (en)	1981-01-15
PL225541A1 (2)	1981-10-30

Publication	Publication Date	Title
DD153840A5 (de)	1982-02-03	Verfahren zur herstellung von neuartigen substituierten pyrazol(1,5-a)pyrimidinen
DE2614406C2 (2)	1992-02-20
DE69936998T2 (de)	2008-05-21	Pyrazolotriazinderivate als gaba-rezeptorliganden
DE69916578T2 (de)	2005-03-31	Pyrazolotriazine als crf-antagonisten
DE69200160T2 (de)	1994-09-15	Angiotensin-II-Antagonisten.
DD150466A5 (de)	1981-09-02	Verfahren zur herstellung substituierter 3-alkyl-6-phenyl-1,2,4-triazolo[4,3-a]pyridine
DE2237765A1 (de)	1973-02-08	Neue aminoderivate von pyrazolo (3,4-b)pyridin-5-carbonsaeuren mit deren estern und salzen, verfahren zu ihrer herstellung und ihre verwendung
DE2609486C2 (2)	1988-11-03
EP0115469B1 (de)	1987-05-20	Heterocyclisch ankondensierte Pyrazolo(3,4-d)pyridin-3-one
DD207716A5 (de)	1984-03-14	Verfahren zur herstellung von 1,2,4-triazinen und von pyrazinen
EP0022078B1 (de)	1984-07-25	Pyrazolochinoline, Verfahren zu ihrer Herstellung, und pharmazeutische Präparate enthaltend diese Verbindungen
DE3343922A1 (de)	1984-06-28	Gewisse substituierte pyrazolochinoline, verfahren zu ihrer herstellung, pharmazeutische praeparate enthaltend diese verbindungen und ihre therapeutische anwendung
DD149066A5 (de)	1981-06-24	Benzazepin-derivate
DD210456A5 (de)	1984-06-13	Verfahren zur herstellung von pyrazolopyridin-verbindungen
DD238235A5 (de)	1986-08-13	Verfahren zur herstellung von ringkondensierten pyrazolo/3,4-d/-pyridin-3-on-derivaten
DE2220615A1 (de)	1972-11-16	Neue 1-substituierte 6-Phenyl-4H-s-triazolo-[4,3-a][1,4]-benzodiazepine und Verfahren zu deren Herstellung
DE3427823A1 (de)	1985-02-07	5-subst.-(1,2,4) triazolo (1,5-c) pyrimidin-2-amine
AT395154B (de)	1992-10-12	Verfahren zur herstellung von neuen imidazo(1,5-a)(1,4)diazepinverbindungen
DE2435041C3 (de)	1978-10-19	8-Substituierte 6-Aryl-4H-s-triazolo [3,4c] thieno [23e] 1,4-diazepine, Verfahren zu ihrer Herstellung, ihre Verwendung in Arzneimitteln und diese enthaltende pharmazeutische Präparate
AT395152B (de)	1992-10-12	Verfahren zur herstellung von neuen imidazo (1,5-a)(1,4)diazepinverbindungen
DE2445430C3 (2)	1979-01-18
EP0084155A2 (de)	1983-07-27	(1,2)-anellierte 1,4-Benzodiazepin-Verbindungen sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
CH617937A5 (en)	1980-06-30	Process for the preparation of 8-chloro-1-hydroxymethyl-6-phenyl-4H-imidazo[1,2-a][1,4]benzodiazepine and 8-chloro-1-hydroxymethyl-6-(o-chlorophenyl)-4H-imidazo[1,2-a][1,4]benz odiazepine
CH642374A5 (de)	1984-04-13	Substituierte 1-piperazinyl-triazolo-thieno-1,4-diazepine.
AT395155B (de)	1992-10-12	Verfahren zur herstellung von neuen imidazo(1,5-a)(1,4)diazepinverbindungen